Aberrant type 1 immunity drives susceptibility to mucosal fungal infections

• DOI: 10.1126/science.aay5731
• Publication Date: 2021-01-14T20:06:30Z
• Authors: Timothy J. Break; Vasileios Oikonomou; Nicolas Dutzan; Jigar V. Desai; Marc Swidergall; Tilo Freiwald; Daniel Chauss; Oliver J. Harrison; Julie Alejo; Drake W. Williams; Stefania Pittaluga; Chyi-Chia R. Lee; Nicolas Bouladoux; Muthulekha Swamydas; Kevin W. Hoffman; Teresa Greenwell-...; Vincent M. Bruno; Lindsey B. Rosen; Wint Lwin; Andy Renteria; Sergio M. Pontejo; John P. Shannon; Ian A. Myles; Peter Olbrich; Elise M. N. Ferré; Monica Schmitt; Daniel Martin; ; Daniel L. Barber; Norma V. Solis; Luigi D. Notarangelo; David V. Serreze; Mitsuru Matsumoto; Heather D. Hickman; Philip M. Murphy; Mark S. Anderson; Jean K. Lim; Steven M. Holland; Scott G. Filler; Behdad Afzali; Yasmine Belkaid; Niki M. Moutsopoulos; Michail S. Lionakis
• Keywords: Male; T-Lymphocytes; Mice; Receptors; Candida albicans; Medicine and Health Sciences; 2.1 Biological and endogenous factors; Aetiology; Polyendocrinopathies, Autoimmune; Immunologic Surveillance; Inbred BALB C; Mucosal; Mice, Inbred BALB C; 0303 health sciences; Interleukin-17; Candidiasis, Chronic Mucocutaneous; Candidiasis; Life Sciences; Middle Aged; 3. Good health; Infectious Diseases; STAT1 Transcription Factor; Female; Infection; Genomics and Computational Biology Core; Adult; Adolescent; General Science & Technology; 610; Chronic Mucocutaneous; Autoimmune Disease; Young Adult; Interferon-gamma; 03 medical and health sciences; Animals; Humans; Immunity, Mucosal; JMG; Aged; Janus Kinases; Animal; Inflammatory and immune system; Interleukins; Immunity; Mouth Mucosa; Disease Models, Animal; Emerging Infectious Diseases; Polyendocrinopathies; Disease Models; Autoimmune

Type 1 immunity gives fungi a foothold

Type 17 immune responses play a vital role against fungal infections of the mucosa. It remains unclear whether other types of immune responses can also contribute to host defense against these pathogens. The yeast Candida albicans prominently infects patients with autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED), an inherited disease caused by loss-of-function mutations in the AIRE gene. Break et al. report that the oral susceptibility of Aire -deficient mice to C. albicans is not due to aberrant type 17 responses. Rather, the overproduction of interferon-γ by local CD4 + and CD8 + T cells in these mice disrupts the epithelial barrier, which increases susceptibility to C. albicans invasion. Similar type 1 immune pathways are operational in APECED patients. Inhibition of interferon-γ or the JAK-STAT signaling pathway in mice ameliorates disease symptoms, suggesting potential future therapeutic interventions for certain classes of fungal disease.

Science , this issue p. eaay5731